2.5- Dimethyl-4- anisole

A mixture of 205 g POCl, and 228 g N-methylformanilide was allowed to incubate at room temperature until there was the development of a deep claret color with some spontaneous heating. To this, there was added 70.8 g 2,3-dimethyl-anisole, and the dark reaction mixture heated on the steam bath for 2.5 h. The product was then poured into 1.7 L H20, and stirred until there was a spontaneous crystallization. These solids were removed by filtration, H20 washed and air dried to give 77.7 g of crude benzaldehyde as brown crystals. This was distilled at 70-90 °C at 0.4 mm/Hg to give 64.8 g of 2,3-dimethyl-4-methoxybenzaldehyde as a white crystalline product with a mp of 51 -52 °C. Recrystallization from MeOH produced ananalyticalsamplcwithampof55-55.5°C. Anal.(C 0H12O2)C,H. Themalononitrile derivative (from the aldehyde and malononitrile in EtOH with a drop of triethylamine) had a mp of 133-133.5 °C from EtOH. Anal. (C Hl2N20) C,H,N. Recently, this aldehyde has become commercially available. 

An improved synthesis of glutinosone (1) was also accomplished by Masamune and coworkers6 and this was based on procedure developed by Dastur7,8 for the synthesis of sesquiterpenes nootkatone. (Scheme 2) Diels-Alder reaction of 3,6-dihydro-3,5-dimethyl anisole with methyl acrylate in absence of Lewis acids afforded a 1 3 mixture of esters (17) and (18) which were converted to a,(3-unsaturated aldehydes (19) in 77% yield by oxidation with selenium (IV) oxide in dioxane. Wittig reaction of aldehydes under the usual condition yielded the dienes (20) in 63% yield which on being subjected to Grignard reaction with an excess of methyllithium produced tettiary alcohols (21) in quantitative yield. This on treatment with formic acid at room temperature gave bicyclic enone (22) and its formate (23) in 45% and 41% yield respectively. Formates (23) were hydrolyzed to enone (22) in 88% yield. 

Not only anisole and methyl anisoles but also cresols and xylenols are formed. In a typical experiment, a product composition, in mol%, is 37.3% unreacted phenol, 37.2% anisole, 9.7% methyl anisoles, 1% dimethyl anisoles, 10.4% cresols and 4.4% xylenols. The C-methylated products were shown to occur via fast initial 0-methylation of the phenol followed by an inter-molecular rearrangement of the aryl methyl ethers to methyl phenols (28). 

Preparation by Friedel-Crafts acylation of 2,6-dimethyl-anisole with p-chlorobenzoyl chloride in the presence of aluminium chloride [902]. 

If this mechanism operated, the presence of compounds such as 2,6-dimethyl-anisole would lead to chain termination ... 

Add the dimethyl sulphate dropwise during 1 hour whilst stirring the mixture vigorously. Then reflux for 2 hours, with stirring, in order to complete the methylation. Allow to cool, add water, transfer to a separatory funnel, remove the lower layer, and wash once with water, twice with dilute sulphuric acid, and then with water until the washings are neutral to litmus. Add some sodium chloride to each washing as this will facilitate the separation of the two layers for anisole is 0- 996). Dry over anhydrous calcium chloride or magnesium sulphate, and distil from an air bath. Collect the anisole at 151-154°. The yield is 40 g. 

The equihbrium constant for this reaction is 1.029 at 25°C and reflux may be accompHshed by decomposing the complex with heat and by absorbing BF in anisole. This system, in contrast to the dimethyl ether—BE system, is a tme gas—Hquid exchange system and contains no associated complex in the gas phase (30). 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

CF3CO2H, PhSCH3, 25°, 3 h. ° The use of dimethyl sulfide or anisole as a cation scavenger was not as effective because of side reactions. Benzyl ethers of serine and threonine were slowly cleaved (30% in 3 h complete cleavage in 30 h). The use of pentamethylbenzene had been shown to increase the rate of deprotection of 0-Bn-tyrosine. ... 

Mix I gram of phenol with i c.c. of dimethyl sulphate and add 4 c.c. of a lo per cent, solution of caustic soda. Warm and shake. The odour of phenol is replaced by that of anisole, which can be extracted from the licjuid by ether (Ullmann s reaction). See Appendix. p. 294. 

Alkyl phenyl ethers (except anisole) Dimethyl pyrroles... 

Feldman and Eastman have suggested that the kinamycins may by reductively activated to form reactive vinyl radical (25) and orf/to-quinone methide (26) intermediates (Scheme 3.2c) [16]. The authors provided convincing evidence that the alkenyl radical 25 is generated when the model substrate dimethyl prekinamycin (24) is exposed to reducing conditions (tri-n-butyltin hydride, AIBN). Products that may arise from addition of this radical (25) to aromatic solvents (benzene, anisole, and benzonitrile) were isolated. The ort/io-quinone methide 26 was also formed,... 

The presence of three hydroxyl groups per glucose unit was shown by the preparation of a triacetate and a tribenzoate. Six or seven methyla-tions (using dimethyl sulfate and concentrated alkali) of dextran did not raise the methoxyl content above 41% (theoretical maximum 45.6%). Also, Purdie methylations (using methyl iodide and silver oxide) and methylation with thallium ethoxide and methyl iodide were ineffective in raising the methoxyl content of methylated dextran above 43.5%. The maximum theoretical methoxyl content was eventually attained by modified Muskat methylations. 6 Partially methylated dextran suspended in anisole solution was treated with sodium in liquid ammonia, and the sodium salt of methylated dextran thus formed was allowed to react with methyl iodide. The methoxyl content of the partially methylated dextran was raised by three such methylations from 42% to 45.5% and by five such methylations from 30% to 45.4%. 

Iodination versus chlorination. Three distinct classes of halogenation reactions are observed with various substituted methoxybenzenes and IC1 when carried out under an identical set of conditions, i.e., exclusive iodination, exclusive chlorination, and mixed chlorination and iodination. For example, equimolar mixtures of anisole, 2,5-dimethyl-1,4-dimethoxybenzene and 1,4-dimethoxybenzene and iodine monochloride (kept in the dark) yield p-iodoanisole, chloro-2,5-dimethyl- 1,4-dimethoxybenzene, and a (4 6) mixture of chloro- and iododimethoxybenzene, respectively, in nearly quantitative yields,225 i.e.,... 

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